Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

Abstract

Methamphetamine (METH) is a highly addictive stimulant, and METH exposure can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. The ever-increasing levels of METH abuse worldwide have necessitated the identification of effective intervention strategies to protect the brain against METH-induced neurotoxicity. The protective effects of molecular hydrogen on oxidative stress and related neurodegenerative diseases have been recently elucidated. Herein, we investigated whether treatment with molecular hydrogen ameliorated the METH-induced neurotoxicity and spatial learning and memory impairments. Male C57BL/6 mice received four intraperitoneal METH injections (10 mg/kg, 3-h interval), and stereotypic behaviors and hyperthermia were observed. After METH treatment and behavioral observation, the mice were returned to their home cages, where they received water or hydrogen-rich water (HRW) ad libitum for 7 days. We found that the molecular hydrogen delivered by ad libitum HRW consumption significantly inhibited the METH-induced spatial learning impairment and memory loss evidenced in the Barnes maze and Morris water maze tests. Furthermore, molecular hydrogen significantly restrained the neuronal damage in the hippocampus after high-dose METH exposure. Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the hippocampus. These are the first findings to indicate that hydrogen might ameliorate METH-induced neurotoxicity and has a potential application in reducing the risk of neurodegeneration frequently observed in METH abusers.

Bi-enzymes treatments attenuate cognitive impairment associated with oxidative damage of heavy metals

“…The water maze consisted of an off-white circular pool (80 cm in diameter) with the upper part surrounded by a 40 cm-high Perspex wall and filled with water at 25 ± 1°C [ 29 ]. The circular pool was segmented into four quadrants and enclosed in a curtain.…”

Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine

“…MA exposure can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. 45,46 MA may become addicted once taken, and addictive symptoms may appear after short-term use. Long-term or highdose use of MA causes abnormalities in the structure, chemistry, and function of brain, resulting in some associated medical complications and fatalities.…”

The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride

“…Molecular hydrogen, as a novel healthcare product for a wide range of diseases, has recently become increasingly popular because of its unique anti-oxidative capability of selectively scavenging highly cytotoxic oxygen radicals and its anti-inflammatory properties ( Qi et al, 2021 ). Our previous studies have revealed that molecular hydrogen delivered by ad libitum hydrogen-rich water (HRW) consumption significantly inhibited METH-induced spatial memory impairment in the Barnes and Morris water maze tests ( Wen et al, 2019 ). In addition, hydrogen-rich saline (HRS) injections attenuated symptoms of low dose METH-induced behavioral sensitization ( Wen et al, 2020 ).…”